The combined use of synthetic organic, biochemical, spectroscopic, and X-ray crystallographic techniques are applied towards gaining detailed information on (and possible manipulative control over) the stereochemical basis of the co-operative oxygenation reaction in human hemoglobin. High resolution (2.5 A-1) atomic coordinates of human deoxyhb and the resulting detailed stereochemical picture of deoxyhb's organic phosphate allosteric effector binding site are used as a unique guide in synthesizing potentially useful allosteric effector-drug analogues which are capable of a more profoundly altering the oxygen transport function of the protein than even 2,3-DPG itself. The resulting irreversible drug-effector: deoxyhb complexes are used both in oxygen equilibrium studies to determine their potential usefullness in counteracting a number of syndromes known to be associated with hypoxia, and in X-ray difference Fourier studies to determine the structure-function properties of partially ligated intermediate hb states. The complexes, as well as other forms of hb (e.g., abnormal human mutant forms and hybrid hbs), will be used as structure function probes in a series of combined X-ray crystallographic, far IR, and resonance Raman spectral studies to investigate recent theories relating Fe-N bond tension at the hemes with cooperative oxygenation phenomena in the presence and absence of allosteric effectors.